An influenza virus causes infectious acute febrile respiratory illness in a host. When the influenza virus is epidemic, it can easily spread across borders due to its strong infectiousness. Also, it may be unpredictably variously mutated, thereby causing interspecific infection. Thus, it is necessary to provide worldwide common countermeasures and monitoring systems.
An influenza virus is taxonomically defined as a member of Orthomyxovirus, and has three types of A, B, and C. Especially, A, and Btypes are epidemically spread. Type A influenza has a high mutatability, and zoonotically infects birds, pigs, and horses, as well as humans. Furthermore, the type A influenza includes various subtypes according to a combination of surface antigens (HA and NA). Unlike type A influenza, type B influenza causes relatively light symptoms, and infects humans and seals. Especially, in humans, it mainly causes an illness in children. Type C influenza can infect humans and pigs, but is known to have relatively low pathogenicity to humans. On the surface of these viruses, two kinds of surface antigens (that is, glycoproteins of Hemagglutinin (HA) and Neuraminidase (NA)) exist. Also, within the viruses, 8 fragmented RNAs exist. Hemagglutinin has a trimer structure including a head and a stem. The head region is related to most antigen mutations, which attaches the virus to a host cell by binding to a terminal sialic acid residue on the surface of the host cell, and sequentially allows the virus to penetrate the host cell. Neuraminidase is a mushroom-shaped tetramer with a head and a stem. On the surface of the head, an active region exists, which cleaves the alpha-ketosidic bond linking a terminal neuraminic acid residue to the oligosaccharide moiety on the cell surface. This cleavage performs an important role when a replicated and propagated virus within the infected cell comes out from the host cell and penetrates a respiratory organ mucous membrane cell. Surface antigens of a virus are mutated in the same subtype, and a new antigen mutant strain appears annually. Especially, from among influenza viruses, an avian influenza virus that has been problematic recently, infects various kinds of birds such as chickens, turkeys, ducks and wild birds through antigenic shift and quickly spreads. When chickens are infected with the virus, the morality rate is 80% or more. Thus, it is a virus causing serious damage and threatening the poultry farming industry worldwide. Further, it is reported that its ripple effect is not limited to the poultry farming industry. In other words, the virus may spread to humans by infecting a human body. Accordingly, research on the treatment of a virus may include inhibition of adsorption into an epithelial cell, inhibition of penetration into a cell, inhibition of transcription and replication of a gene, inhibition of protein synthesis, inhibition of release from a cell, and the like. Each of these is an objective of development of a novel antiviral drug.
TABLE 0STRUCTURE 1. Amantadine STRUCTURE 2. Rimantadine  STRUCTURE 3. Oseltamivir Phosphate STRUCTURE 4. Zanamivir
Conventionally developed representative therapeutic agents for treating an influenza virus include 4 materials such as Amantadine, Rimantadine, Zanamivir, and Oseltamivir, which were approved by the US Food and Drug Administration (FDA) (see STRUCTURES 1 to 4). Amantadine or Rimantadine is an M2 ion channel blocker having activity only against a Hemagglutinin virus strain (an influenza virus), and interrupts replication of a virus particle introduced into a host cell. These drugs are effective in only type A influenza virus A. Also, since they have been used for 40 years, it is known that a virus resistant to the drugs has been generated, and the drugs cause serious side effects in the nervous system and the stomach. Meanwhile, Oseltamivir (Korean Patent Publication No. 10-1998-0703600) or Zanamivir (Korean Registered Patent 0169496) is a Neuraminidase inhibitor having activity only against a Neuraminidase virus strain (influenza virus) and interrupts a replicated virus from escaping from a host cell. The two kinds of therapeutic agents intervene in one process of influenza virus infection and interrupt the process, thereby inhibiting of the propagation of a virus. However, Zanamivir has a high antiviral effect, but has disadvantages such as a low bioavailability and a quick release from the kidney. Also, in Oseltamivir, there have been reported some side effects such as generation of a resistant virus, and serious emesis symptoms.
Following these drugs used as antiviral therapeutic agents, mutant viruses having serious side effects, tolerance, and strong resistance have rapidly appeared recently. Thus, their application requires great care. Also, in the development of a vaccine, there is a problem in that when an epidemic virus type does not correspond to a virus of the vaccine, the effect is insignificant. Accordingly, it is highly required to develop an improved drug that has a high effect in treatment and prevention of influenza infection, and has a high stability.